The present invention is concerned with a nucleic acid sequence encoding a Marek's Disease virus polypeptide, a recombinant nucleic acid molecule comprising such a nucleic acid sequence, a vector virus comprising said nucleic acid sequence, a host cell transformed with such a nucleic acid sequence, a Marek's Disease virus polypeptide and antibodies reactive therewith, as well as a vaccine against Marek's Disease.
Marek's Disease (MD) is a malignant, lymphoproliferative disorder of domestic fowl caused by a herpesvirus: Marek's Disease Virus (MDV). MD is ubiquitous, occurring in poultry-producing countries throughout the world. Chickens raised under intensive production systems will inevitably suffer losses from MD. MD affects chickens from about 6 weeks of age, occurring most frequently between ages of 12 and 24 weeks.
Three forms of MD are recognized clinically, classical MD, acute MD and transient paralysis.
Classical MD is characterized by peripheral nerve enlargement caused by lymphoid infiltration and demyelination, and paralysis is the dominant clinical sign. Mortality is variable but normally under 10-15 percent.
In the acute form there are multiple and diffuse lymphomatous tumors in the visceral organs. Mortality from this form of MD is usually higher than from the classical form. An incidence of 10-30 percent is common in unvaccinated flocks and outbreaks involving up to 70% of the flock may be encountered. The pathological lesions in both classical and acute MD are essentially similar, involving the proliferation and infiltration of malignantly transformed T-lymphoblasts into normal tissues, peripheral nerves in the case of the classical form and visceral organs in the case of the acute form.
Furthermore, the MDV has been shown to be responsible for encephalitis of young chickens characterized by sudden paralysis.
Serological classification of MD related viruses yielded three serotypes:
______________________________________ Type I naturally occurring virulent strains of Marek's disease virus which are pathogenic and tumorigenic to chickens, and attenuated nonpathogenic strains derived therefrom Type II naturally occurring nonpathogenic strains of Marek's disease virus; and Type III herpesvirus of turkeys ("HVT"), which is nonpathogenic to chickens. ______________________________________
Serial passage of pathogenic strains of MDV serotype I was found to result in loss of pathogenicity and oncogenicity, but not of immunogenicity. Attenuated strains derived from HPRS-16 and CVI-988 strains have been applied as vaccines. SB-I and HN-I MDV strains (serotype 2) have also been shown to be useful in vaccination. HVT, first isolated from turkeys, is apathogenic in turkeys and domestic fowls, antigenically related to serotype 1 and 2 MD viruses and extensively used as a vaccine against MD.
There are no methods of treatment of MD and control is based on management methods which isolate growing chickens from sources of infection, the use of genetically resistant stock, and vaccination. However, management procedures are normally not cost-effective and the progress has been disappointing with respect to the selection of poultry stock with increased genetically controlled resistance. Nowadays, control of MD is almost entirely based on vaccination.
Current vaccines comprise chemically inactivated virus vaccines or modified live-virus vaccines. However, inactivated vaccines require additional immunizations, disadvantageously contain adjuvants, are expensive to produce and are laborious to administer. Further, some infectious virus particles may survive the inactivation process and may cause disease after administration to the animal.
In general, attenuated live virus vaccines are preferred because they evoke an immune response often based on both humoral and cellular reactions. Up to now, such vaccines based on MDV serotype I strains could only be prepared by serial passage of virulent strains in tissue culture. However, because of this treatment uncontrolled mutations are introduced into the viral genome, resulting in a population of virus particles heterogeneous with regard to virulence and immunizing properties. Overattenuation during passage in cell culture can also be a problem with these vaccines. One must achieve a delicate balance between ensuring that the vaccine is not virulent while making certain that it is still protective. In addition it is well known that such traditional attenuated live virus vaccines can revert to virulence resulting in disease outbreaks in inoculated animals and the possible spread of the pathogen to other animals. The occurrence of very virulent field strains of MD virus against which live HVT vaccines provided poor protection have now been isolated and are responsible for excessive losses in various parts of the world. Bivalent vaccines consisting of serotype 2 and serotype 3 strains are reasonably effective against very virulent field isolates in some cases. Multivalent vaccines containing serotype antigens should be even more effective at eliciting immunity against these very virulent strains.
Improved vaccines might be constructed based on recombinant DNA technology. These vaccines would only contain the necessary and relevant MDV immunogenic material which is capable of eliciting a protective immune response against the MDV pathogens, or the genetic information encoding said material, and would not display above mentioned disadvantages of the live or inactivated vaccines.